Christopher BROWN

Email: CJBrown[at]imcb.a-star.edu.sg  Lab Location: Neuros #06-04/05  Tel: 64070559

The main focus of our team’s activities is to discover novel modalities such as macrocyclic peptides and mini-proteins in order to perturb intracellular biological interactions of therapeutic interest. In particular, we focus on targeting macromolecular surfaces that are considered to be intractable to small molecule binding.  

We use a variety of display technologies such as chemically modified phage and yeast libraries to efficiently search chemical and structural space to discover and isolate these molecules, which are then characterised using biophysical and structural methods. 

We are highly interested in developing techniques that extend the functionality of these molecules and allow these molecules to be delivered to their targets to enable target validation and therapeutic modelling studies. For example:

An attractive use of mini-proteins is that these modalities can be expressed in 3D cellular culture and animal systems to model the potential cellular effects of their interaction sites. If these molecules induce desirable phenotypes they can then be used as structural templates for therapeutic discovery programs.  

The fusion of miniproteins with protein domains of orthogonal functionality that can extend their use beyond conventional event driven modes of inhibition, such as E3 ligases, whereby multiple target molecules can be catalytically degraded by a single modality.